The objective of this proposal is to investigate the teratogenic effects of ethanol exposure at a time equivalent to the human third trimester, on the development of the central nervous system (CNS). Elucidation of third semester effects has obvious theoretical and potential practical importance, yet it has received little attention. The hippocampal formation of the rat will be used as the model system for assessing CNS changes, since more is known about its development and its relatively simple anatomical organization than possibly any other brain region. However, the rat brain is less developed at birth than the human brain; development equivalent to the human third trimester occurs in the rat during the first 10 days postpartum. In order to provide neonatal rats with proper nutrition while exposing them to controlled amounts of ethanol, a special gastrostomy artificial feeding procedure will be used. Preliminary studies using this technique have confirmed that early postnatal ethanol exposure results in topographical alterations in the terminal field of the hippocampal mossy fiber system. Focusing on this aberrant organization, two fundamental questions related to the etiology of the fetal alcohol syndrome will be addressed. First, what is the extent of the structural alterations in the hippocampal formation following heavy ethanol exposure during the developmental period equivalent to the third trimester? Second, what is the minimum ethanol dose necessary to produce detectable alterations in hippocampal organization during the same period? Data will also abe gathered to determine whether the effects of ethanol exposure are more pronounced in males or females. Light microscopic techniques, including the Timm's stain and horseradish peroxidase (HRP) histochemistry will be employed to detect ethanol-induced changes in the characteristic laminar differentiation of the afferent fiber systems in the hippocampal formation. A quantitative analysis of pyramidal and granule cells will also be made. These experiments should provide basic information concerning the vulnerability of the developing brain to ethanol exposure during a time equivalent to the human third trimester, and may generate data that will be useful in establishing guidelines for safe levels of alcohol consumption by pregnant women.